He then joined the George S. Wise Faculty of Life Sciences at Tel Aviv University. His research field is structural bioinformatics.

Since their emergence about 3.7 billion years ago, proteins have been key to life as we know it. But how did they emerge and continue to evolve? The straightforward path, involving the addition of one amino acid after another—starting from scratch, is bound to fail, as the vast majority of such arbitrary strings can't even form stable structures, which are essential to function. Therefore, instead, evolution follows a cut-and-paste approach, where amino acid segments from existing proteins are grafted and stitched together to form new proteins. We know this, because the latter approach leaves traces, in the form of reused segments, which we detect, and call ‘themes’. By tracing these, we aim to decipher the origin of proteins, similar to archeologists tracing human history. Some of the themes are shared between ancient proteins that differ in their function and architecture. For example, we detect themes at the interface of the ferredoxin, Rossmann, and P-loop domains.

A related question is how did protein-ligand recognition emerge and continues to evolve? To address it we conducted an in-depth analysis of protein-adenine interaction. Adenine is a triangle-like structure that has three hydrogen donor/acceptor edges, and previous studies noted that only one of these, the famous Watson-Crick edge, facilitates protein binding. Our analysis shows that the two other edges also bind proteins, which makes sense in view of the opportunistic nature of evolution. Furthermore, we see that adenine binding is often mediated by the above themes, in support of their contribution to the emergence and evolution of proteins. The talk will cover the work published in Nepomnyachiy et al., PNAS 2014 (PMID: 25071170) and 2017 (PMID: 29078314)), and current continuation.

Relevant publications

• S. Nepomnyachiy, N. Ben-Tal*, R. Kolodny* (2014). Global view of the protein universe. Proc. Natl. Acad. Sci. USA 111: 1691–11696.

• S. Nepomnyachiy, N. Ben-Tal*, R. Kolodny* (2017). Complex evolutionary footprints revealed in an analysis of reused protein segments of diverse lengths. Proc. Natl. Acad. Sci. USA 114:11703-11708.